Introduction

Principles, Objectives & Scope of Today’s Session

🙏 THANK YOU

  • 15 experts completed the pre-meeting questionnaire
  • 11 experts joined the first session (27 November)
  • Thank you for your valuable contribution to the CRF refinement process

Guiding Principles

  • Safe and inclusive space
  • Shared vision & common goal
  • Consensus-driven process
  • Respectful, equal participation
  • Short, focused interventions

Approach

We systematically reviewed all feedback from the 27 November expert session, including:

  • Redefining and clarifying variables
  • Reorganizing sections for coherence
  • Proposals for additions or removals
  • Consolidating outstanding questions

Objectives

  • Review all CRF items, focusing on pending questions
  • Clarify open issues raised by the expert group
  • Confirm areas of emerging agreement

Outside Today’s Scope

  • We will not make definitive decisions here and now:
  • Final CRF structure & content will be shaped
  • after WHO reviews all expert inputs
  • and integrates consolidated recommendations.

Variables for Discussion 1.0

Demographics/Baseline

Is the patient currently pregnant or was pregnant in the last 6 weeks?

  • Pregnancy: experts agreed to retain Pregnancy as a core variable.

Vitals

Capillary refill ≥ 3 sec

Temperature

Shock

  • defined by:
    • Blood pressure
    • Capillary refill
    • Cold peripheries
  • All listed vital signs were considered important for assessing shock, and a separate shock item was added.
  • A clear and consistent definition will need to be included

Level of consciousness

  • Level of consciousness: Discussion is needed on whether AVPU or GCS should be retained as the preferred assessment tool.

Height/Weight

Respiratory rate

  • Definition of shock: All listed vital signs were considered important for assessing shock, and a separate shock item was added.
    • A clear and consistent definition will need to be included
  • Level of consciousness: Discussion is needed on whether AVPU or GCS should be retained as the preferred assessment tool.
  • Definition of obesity: Height and weight were not retained in this section. Obesity has been added under comorbidities, but its operational definition still needs to be discussed and agreed upon.
  • Overall, all need to be included, and considered more important that symptoms
  • Shock: Highly important. Needs to be carefully defined, needs further discussion
  • Capillary refill ≥ 3 sec: Included in paediatric shock definition, and part of WHO guidelines
  • Level of consciousness: discussion on whether to retain AVPU or GCS as the preferred assessment tool.
  • Temperature: highlighted by one expert as an important parameter to include.
  • Shock assessment: capillary refill time and SpO₂ identified as relevant markers of shock.
  • Height/Weight: discussion on inclusion for BMI calculation and to define Obesity (see also comorbities).

Symptoms

Signs of ascites and pleural effusion

Bleeding

❓ WHO Warning Signs

  • Abdominal pain or tenderness
  • Persistent vomiting
  • Clinical fluid accumulation
  • Mucosal bleed
  • Lethargy, restlessness
  • Liver enlargement >2 cm
  • Laboratory: increase in HCT concurrent with rapid decrease in platelet count

Confusion or agitation

Fever

Seizures

  • WHO warning signs: Should this be used as an umbrella category encompassing the symptoms and laboratory findings defined in the WHO classification?
    • Considerations include feasibility, clarity, and whether this grouping sufficiently captures the clinical information needed.
  • Bleeding: Added as a separate variable.
    • Note that Severe Bleeding: Currently considered under complications and as part of the parent term Shock.
    • Panel discussion may clarify whether it should remain a distinct variable.
  • Signs of ascites and pleural effusion: considered important, with discussion on the best way to capture these variables.
  • Fever: suggested for exclusion by some experts.Non-discrimatory, Also captured by temperature
  • Seizures: suggested for exclusion by some experts due to difficulty/reliability of recollection.
  • WHO warning signs: could serve as an umbrella term to include persistent vomiting and abdominal pain; importance of balancing feasibility, accuracy, and clinical relevance was emphasized.
  • Bleeding: discussion on whether to include as a symptom.

Comorbidities

Diabetes (type 1 or type 2)

Obesity

Hypertension

Obesity

❓ Chronic kidney disease

❓ Chronic heart disease (e.g., heart failure, coronary artery disease)

❓ Chronic liver disease

❓ Immunosuppressive condition or Immunosuppressive medication

Cancer diagnosis

Fever

Bleeding disorder or take anticoagulant/antiplatelet medication

  • Chronic liver disease, chronic cardiac disease, and chronic kidney disease:
    • Should these conditions be considered mandatory variables to capture?
    • Experts noted the challenges related to their definition, consistent classification, and reliable recollection by patients or caregivers.
  • Immunosuppressive condition or Immunosuppressive medication:
    • Experts noted the challenges related to its strict definition.
  • Obesity:
    • Experts expressed the need to capture this variable.
    • Requires clear and strict definition criteria.
  • Obesity: discussion on inclusion; also noted the need to retain height and weight for BMI calculation in vitals.
  • Prematurity: suggested for consideration in pediatric patients, though not deemed critical by all experts.
  • Hypertension (HTA): recommended to be added as a comorbidity and moved out of the complications section.
  • Chronic disease: noted challenges in reliable recollection by participants.
  • Cancer: considered for exclusion by some experts

Laboratory and Imagery

Creatinine

❓ DENV serotype

❓ Hematocrit

Blood count results available

Hemoglobin

  • Hematocrit and hemoglobin:
    • Should hematocrit be used as the primary marker for assessing anemia, given its potential advantages over hemoglobin? - Clarification is needed on whether hematocrit should be considered as a standalone criterion.
  • DENV serotype: While acknowledging that serotyping is not available in all settings, it remains a valuable variable when available and can be captured rapidly.
    • The panel should consider whether its inclusion would meaningfully increase the burden on data collectors.
  • DENV serotype: considered important, though acknowledged as not available in all settings.
  • Hemoglobin: experts noted that hematocrit may be a better marker, being less affected by potential hemoconcentration.
  • Creatinine: considered important for defining AKI.
  • Availability of blood count results: suggested for exclusion by some experts.

Complications

Severe Organ Impairment

  • Respiratory Complications. Including but not limited to:
    • Acute Respiratory Distress Syndrome (ARDS)
  • Cardiac Complications. Including but not limited to:
    • Cardiac arrest/ Cardiac arrhythmia / Shock
    • Myocarditis / Pericarditis
  • Liver Complications. Including but not limited to:
    • Acute hepatitis
    • Hepatic encephalopathy (any grade) / Severe liver disease (new onset)
  • Renal Complications. Including but not limited to:
    • Acute renal injury / Acute renal failure
    • Urine flow rate
  • Neurological Complications. Including but not limited to:
    • Encephalitis / Meningitis
    • Focal neurological signs

Fluid Overload

  • Pleural effusion / Ascites

❓ Severe bleeding

Hypertension

Seizure

Sepsis

  • Severe Organ Impairment: Proposal to reclassify variables related to liver dysfunction, cardiac complications, and brain injury under the umbrella term Severe Organ Impairment.
    • Discussion is needed to clarify the boundaries of this definition and which specific conditions or indicators should be included.
  • Severe Bleeding: Also considered under the parent term Shock.
    • Panel discussion needed on whether it should be retained as a separate variable.
  • Severe Organ Impairment: suggested reclassification under the umbrella term Severe Organ Impairment for variables related to liver dysfunction, cardiac complications, and brain injury.
  • Fluid overload: suggested reclassification under the umbrella term Fluid overload for variables such as pleural effusion and ascites.
  • Seizure: suggested for exclusion by some experts.

Treatments

Blood transfusion

Platelets

❓ Diuretics

❓ Highest level of care

❓ Renal replacement therapy (e.g., dialysis)

❓ NSAIDs

Antivirals

Fluid drainage (Therapeutic ascitic/pleural tap

  • Fluid drainage: Experts agreed to remove this variable as it is not routinely performed in practice.
    • Discussion is needed on whether diuretics should be included instead.
  • Antivirals: suggested for exclusion by some experts.
  • Fluid drainage (Therapeutic ascitic/pleural tap included): There was discussion the need to keep as not done in every settings. Use of Diuretic was also mentioned.
  • NSAIDs: In addition to NSAIDs, Paracetamol was mentioned as a possible cause of liver dysfunction

Variables for Discussion 2.0

Demographics/Baseline

  • Is the patient currently pregnant or was pregnant in the last 6 weeks?
  • Pregnancy: experts agreed to retain Pregnancy as a core variable.

Vitals

  • AVPU
  • Capillary refill ≥ 3 sec
  • GCS
  • SpO2
  • Temperature
  • Height/Weight
  • Respiratory rate
  • Shock defined by:
    • Blood pressure
    • Capillary refill
    • Cold peripheries
  • Definition of shock: All listed vital signs were considered important for assessing shock, and a separate shock item was added.
    • A clear and consistent definition will need to be included
  • Level of consciousness: Discussion is needed on whether AVPU or GCS should be retained as the preferred assessment tool.
  • Definition of obesity: Height and weight were not retained in this section. Obesity has been added under comorbidities, but its operational definition still needs to be discussed and agreed upon.
  • Overall, all need to be included, and considered more important that symptoms
  • Shock: Highly important. Needs to be carefully defined, needs further discussion
  • Capillary refill ≥ 3 sec: Included in paediatric shock definition, and part of WHO guidelines
  • Level of consciousness: discussion on whether to retain AVPU or GCS as the preferred assessment tool.
  • Temperature: highlighted by one expert as an important parameter to include.
  • Shock assessment: capillary refill time and SpO₂ identified as relevant markers of shock.
  • Height/Weight: discussion on inclusion for BMI calculation and to define Obesity (see also comorbities).

Symptoms

  • WHO Warning Signs:
    • Abdominal pain or tenderness
    • Persistent vomiting
    • Clinical fluid accumulation
    • Mucosal bleed
    • Lethargy, restlessness
    • Liver enlargement >2 cm
    • Laboratory: increase in HCT concurrent with rapid decrease in platelet count
  • Signs of ascites and pleural effusion
  • Bleeding
  • Confusion or agitation
  • Fever
  • Seizures
  • WHO warning signs: Should this be used as an umbrella category encompassing the symptoms and laboratory findings defined in the WHO classification?
    • Considerations include feasibility, clarity, and whether this grouping sufficiently captures the clinical information needed.
  • Bleeding: Added as a separate variable.
    • Note that Severe Bleeding: Currently considered under complications and as part of the parent term Shock.
    • Panel discussion may clarify whether it should remain a distinct variable.
  • Signs of ascites and pleural effusion: considered important, with discussion on the best way to capture these variables.
  • Fever: suggested for exclusion by some experts.Non-discrimatory, Also captured by temperature
  • Seizures: suggested for exclusion by some experts due to difficulty/reliability of recollection.
  • WHO warning signs: could serve as an umbrella term to include persistent vomiting and abdominal pain; importance of balancing feasibility, accuracy, and clinical relevance was emphasized.
  • Bleeding: discussion on whether to include as a symptom.

Comorbidities

  • Diabetes (type 1 or type 2)
  • Obesity
  • Hypertension (HTA)
  • ❓ Chronic heart disease (e.g., heart failure, coronary artery disease)
  • ❓ Chronic kidney disease
  • ❓ Chronic liver disease
  • ❓ Immunosuppressive condition or Immunosuppressive medication
  • Cancer diagnosis
  • Bleeding disorder or take anticoagulant/antiplatelet medication
  • Chronic liver disease, chronic cardiac disease, and chronic kidney disease:
    • Should these conditions be considered mandatory variables to capture?
    • Experts noted the challenges related to their definition, consistent classification, and reliable recollection by patients or caregivers.
  • Immunosuppressive condition or Immunosuppressive medication:
    • Experts noted the challenges related to its strict definition.
  • Obesity:
    • Experts expressed the need to capture this variable.
    • Requires clear and strict definition criteria.
  • Obesity: discussion on inclusion; also noted the need to retain height and weight for BMI calculation in vitals.
  • Prematurity: suggested for consideration in pediatric patients, though not deemed critical by all experts.
  • Hypertension (HTA): recommended to be added as a comorbidity and moved out of the complications section.
  • Chronic disease: noted challenges in reliable recollection by participants.
  • Cancer: considered for exclusion by some experts

Laboratory and Imagery

  • ❓ DENV serotype
  • Hematocrit
  • Creatinine
  • Blood count results available
  • Hemoglobin
  • Hematocrit and hemoglobin:
    • Should hematocrit be used as the primary marker for assessing anemia, given its potential advantages over hemoglobin? - Clarification is needed on whether hematocrit should be considered as a standalone criterion.
  • DENV serotype: While acknowledging that serotyping is not available in all settings, it remains a valuable variable when available and can be captured rapidly.
    • The panel should consider whether its inclusion would meaningfully increase the burden on data collectors.
  • DENV serotype: considered important, though acknowledged as not available in all settings.
  • Hemoglobin: experts noted that hematocrit may be a better marker, being less affected by potential hemoconcentration.
  • Creatinine: considered important for defining AKI.
  • Availability of blood count results: suggested for exclusion by some experts.

Complications

  • Severe Organ Impairment
    • Respiratory Complications. Including but not limited to:
      • Acute Respiratory Distress Syndrome (ARDS)
    • Cardiac Complications. Including but not limited to:
      • Cardiac arrest/ Cardiac arrhythmia / Shock
      • Myocarditis / Pericarditis
    • Liver Complications. Including but not limited to:
      • Acute hepatitis
      • Hepatic encephalopathy (any grade) / Severe liver disease (new onset)
    • Renal Complications. Including but not limited to:
      • Acute renal injury / Acute renal failure
      • Urine flow rate
    • Neurological Complications. Including but not limited to:
      • Encephalitis / Meningitis
      • Focal neurological signs
  • Fluid Overload
    • Pleural effusion / Ascites
  • ❓ Severe bleeding
  • Hypertension
  • Seizure
  • Sepsis
  • Severe Organ Impairment: Proposal to reclassify variables related to liver dysfunction, cardiac complications, and brain injury under the umbrella term Severe Organ Impairment.
    • Discussion is needed to clarify the boundaries of this definition and which specific conditions or indicators should be included.
  • Severe Bleeding: Also considered under the parent term Shock.
    • Panel discussion needed on whether it should be retained as a separate variable.
  • Severe Organ Impairment: suggested reclassification under the umbrella term Severe Organ Impairment for variables related to liver dysfunction, cardiac complications, and brain injury.
  • Fluid overload: suggested reclassification under the umbrella term Fluid overload for variables such as pleural effusion and ascites.
  • Seizure: suggested for exclusion by some experts.

Treatments

  • Blood transfusion
  • Platelets
  • ❓ Diuretics
  • Antivirals
  • Fluid drainage (Therapeutic ascitic/pleural tap included)
  • ❓ Highest level of care
  • ❓ Renal replacement therapy (e.g., dialysis)
  • ❓ NSAIDs
  • Fluid drainage: Experts agreed to remove this variable as it is not routinely performed in practice.
    • Discussion is needed on whether diuretics should be included instead.
  • Antivirals: suggested for exclusion by some experts.
  • Fluid drainage (Therapeutic ascitic/pleural tap included): There was discussion the need to keep as not done in every settings. Use of Diuretic was also mentioned.
  • NSAIDs: In addition to NSAIDs, Paracetamol was mentioned as a possible cause of liver dysfunction

Thank you